Effects of Verapamil and Its Optical Isomers on Repetitive Slow Responses Induced by Electrical Depolarization in Canine Ventricular Myocardium

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Abstract
The electrophysiological effects of verapamil (racemic compounds) and its optical (d- and l-) isomers on canine ventricular myocardial fibers were investigated in current clamp conditions using single sucrose gap chamber and microelectrodes. The current-voltage (I-V) relationships were obtained in normal and low Na (12 mM)-low Ca (0.45 mM) solutions with and without the drugs. Verapamil and its optical isomers blocked repetitive action potential discharges (slow responses) induced by depolarizing DC-currents but l-isomer was more potent than d-isomer in suppressing these responses. The difference in the potency was attributed to their different actions on the steady state I-V relationships: l-isomer increased time independent membrane conductance to K ions while d-isomer did not. This effect of l-isomer may favor the suppression of phase 4 depolarization and reduce the frequency of repetitive action potential discharges in depolarized ventricular muscle more effectively than d-isomer.